Glutamatergic Mechanisms in Schizophrenia

Annual Review of Pharmacology and Toxicology - Tập 42 Số 1 - Trang 165-179 - 2002
Guochuan Tsai1, Joseph T. Coyle2
1Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
2Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478;,

Tóm tắt

Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.

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Tài liệu tham khảo

10.1016/S0896-6273(00)00111-2

Gottesman II, 1991, Schizophrenia Genesis: The Origins of Madness.

10.1016/S0006-3223(99)00281-4

10.1126/science.7939669

10.1192/bjp.166.5.563

10.1146/annurev.med.46.1.113

10.1016/S0006-3223(99)00018-9

10.1001/archpsyc.56.7.649

Weinberger DR, 1997, Int. Clin. Psychopharmacol., 12, 609, 10.1097/00004850-199709004-00006

10.1016/0301-0082(95)00014-M

10.1176/ajp.152.3.444

10.1176/ajp.157.1.26

10.1016/0893-133X(88)90012-7

10.1001/archpsyc.1990.01810150013003

10.1016/S0006-3223(99)00067-0

10.1016/0893-133X(95)00068-O

10.3109/10673229609017192

Coyle JT, Leski M, Morrison J. 2001. Diverse role of L-glutamate acid in brain signal tranduction. InNeuropsychopharmacology:Fifth Generation of Progress. New York: Lippencott

10.1146/annurev.ne.17.030194.000335

10.1038/325529a0

Kemp JA, 1993, TiPS, 141, 20

10.1073/pnas.96.2.721

10.1016/0922-4106(94)90058-2

Dingledine R, 1999, Pharmacol. Rev., 51, 7

10.1001/archpsyc.1962.01710230063007

10.1176/ajp.148.10.1301

10.1001/archpsyc.1994.03950030035004

10.1016/S0006-3223(99)00097-9

10.1093/hrp/7.3.125

10.1176/ajp.156.10.1646

10.1016/S0006-3223(96)00546-X

10.1097/00001756-199512150-00015

10.1176/ajp.154.6.805

10.1016/S0893-133X(98)00060-8

10.1523/JNEUROSCI.16-06-02034.1996

10.1038/1137

10.1016/0304-3940(80)90178-0

10.1176/appi.ajp.158.9.1367

10.1016/S0006-3223(98)00151-6

10.1001/archpsyc.1995.03950220039008

10.1006/nbdi.1997.0153

10.1016/S0006-3223(01)01078-2

10.1016/0006-8993(94)01384-T

10.1111/j.1471-4159.1989.tb07257.x

10.1016/S0140-6736(88)91371-2

10.1016/0306-4522(90)90219-T

10.1016/0304-3940(83)90046-0

10.1016/S0006-3223(96)00220-X

10.1016/0006-3223(92)90043-Y

10.1016/0006-3223(94)91197-5

10.1016/0169-328X(94)00247-C

10.1016/0006-8993(95)00922-D

10.1016/S0006-8993(96)01404-7

10.1016/S0893-133X(00)00189-5

Akbarian S, 1996, J. Neurochem., 16, 19

10.1176/appi.ajp.157.7.1141

10.1176/appi.ajp.157.11.1811

10.1523/JNEUROSCI.17-08-02921.1997

10.1126/science.281.5381.1349

10.1007/s002130050168

10.1016/0304-3940(93)90641-W

10.1016/0024-3205(93)90496-P

10.1016/S0006-3223(00)00976-8

10.1016/S0893-133X(97)00092-4

10.1016/S0022-3956(99)00031-X

10.1016/0006-8993(95)01241-9

10.1176/ajp.148.11.1474

10.1111/j.1471-4159.1993.tb13387.x

Moghaddam HPJ, 1994, J. Neurochem., 63, 785, 10.1046/j.1471-4159.1994.63020785.x

10.1016/0166-2236(90)90108-M

10.1016/S0092-8674(00)81972-8

10.1146/annurev.pa.30.040190.000403

10.1176/ajp.151.8.1234

10.1192/bjp.169.5.610

10.1016/0006-3223(95)00585-4

10.1001/archpsyc.56.1.29

10.1016/S0006-3223(98)00279-0

10.1152/ajplegacy.1971.221.6.1629

10.1016/0006-8993(90)90745-W

10.1016/0304-3940(89)90379-0

10.1176/ajp.152.5.815

10.1016/S0006-3223(96)00311-3

10.1007/BF01276429

10.1097/00002826-199619050-00008

10.1016/S0893-133X(99)00014-7

10.1017/S1461145798001242

10.1001/archpsyc.56.1.21

Tsai G, 1999, Am. J. Psychiatry, 156, 1822, 10.1176/ajp.156.11.1822

10.1176/ajp.153.12.1628

Johnson SA, 1999, J. Pharmacol. Exp. Ther., 289, 392

10.1016/S0006-8993(96)01049-9

Goff DC, 1999, Schizophrenia Res., 36, 280

10.1126/science.2660263

10.1126/science.283.5398.70

10.1126/science.1835799

10.1016/S0022-3476(80)80447-1

10.1016/0006-3223(93)90265-F

10.1001/archpsyc.1995.03950240016004

10.1016/S0022-3956(97)00014-9

10.1038/24790

10.1016/S0960-9822(00)80043-3